Challenges in Application of Langmuir Monolayer Studies To Determine the Mechanisms of Bactericidal Activity of Ruthenium Complexes

The effects induced by antibiotics on the bacterial membrane may be correlated with their bactericidal activity, and such molecular-level interactions can be probed with Langmuir mono layers representing the cell membrane. In this study, we investigated the interaction between {[}Ru(nicbtz)(2)(PPh3)(2)] (RuBTZ, mcbtz = 2-mercaptobenzothiazoline) and {[}Ru(mctz)(2)(PPh3)(2)] (RuCTZ, mctz = 2-mercaptothiazoline) with Langmuir monolayers of a lipid extract of Escherichia coli, an extract of lipopolysaccharides (LPSs), and a zwitterionic phospholipid, dioleoylphosphatidyl choline (DOPC). RuBTZ and RuCTZ had little effects on DOPC, which is consistent with their negligible toxicity toward mammalian cells that may be approximated by a zwitterionic monolayer. Also little were their effects on LPSs. In contrast, RuBTZ and RuCTZ induced expansion in the surface pressure isotherms and decreased the compressional modulus of the E. coli lipid extract. While the more hydrophobic RuBTZ seemed to affect the hydrophobic tails of the E. coli extract monolayer to a larger extent, according to polarization modulation infrared reflection absorption spectroscopy results, evidence of a stronger RuBTZ interaction could not be confirmed unequivocally. Therefore, the interaction with the E. coli cell membrane cannot be directly correlated with the observed higher bactericidal activity of RuBTZ, in comparison to that of RuCTZ. This appears to be a case in which Langmuir monolayer studies do not suffice to determine the mechanisms responsible for the bactericidal activity. (AU)